Legionella pneumophila induces human beta Defensin-3 in pulmonary cells

<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila </it>is an important causative agent of severe pneumonia in humans. Human alveolar epithelium and macrophages are effective barriers for inhaled microorganisms and actively participate in the initiation of innate host defense. The beta defensin-3 (hBD-3), an antimicrobial peptide is an important component of the innate immune response of the human lung. Therefore we hypothesize that hBD-3 might be important for immune defense towards <it>L. pneumophila</it>.</p> <p>Methods</p> <p>We investigated the effects of <it>L. pneumophila </it>and different TLR agonists on pulmonary cells in regard to hBD-3 expression by ELISA. Furthermore, siRNA-mediated inhibition of TLRs as well as chemical inhibition of potential downstream signaling molecules was used for functional analysis.</p> <p>Results</p> <p><it>L. pneumophila </it>induced release of hBD-3 in pulmonary epithelium and alveolar macrophages. A similar response was observed when epithelial cells were treated with different TLR agonists. Inhibition of TLR2, TLR5, and TLR9 expression led to a decreased hBD-3 expression. Furthermore expression of hBD-3 was mediated through a JNK dependent activation of AP-1 (c-Jun) but appeared to be independent of NF-κB. Additionally, we demonstrate that hBD-3 elicited a strong antimicrobial effect on <it>L. pneumophila </it>replication.</p> <p>Conclusions</p> <p>Taken together, human pulmonary cells produce hBD-3 upon <it>L. pneumophila </it>infection via a TLR-JNK-AP-1-dependent pathway which may contribute to an efficient innate immune defense.</p

International Comparisons of Behavioral and Emotional Problems in Preschool Children: Parents' Reports From 24 Societies

International comparisons were conducted of preschool children's behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 11/2-5 by parents in 24 societies (N=19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders-oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3-12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0-198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies